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Retinoic acid receptor alpha

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Title: Retinoic acid receptor alpha  
Author: World Heritage Encyclopedia
Language: English
Subject: Nuclear receptor related-1 protein, Small heterodimer partner, Zinc finger and BTB domain-containing protein 16, Retinoid X receptor alpha, Nuclear receptor
Collection: Intracellular Receptors, Transcription Factors
Publisher: World Heritage Encyclopedia

Retinoic acid receptor alpha

Retinoic acid receptor, alpha

PDB rendering based on 1dkf.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; NR1B1; RAR
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a nuclear receptor that in humans is encoded by the RARA gene.[1][2]


  • Function 1
  • Clinical significance 2
  • Interactions 3
  • See also 4
  • References 5
  • Further reading 6


Retinoid signaling is transduced by 2 families of nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), which form RXR/RAR heterodimers. In the absence of ligand, DNA-bound RXR/RARA represses transcription by recruiting the corepressors NCOR1, SMRT (NCOR2), and histone deacetylase. When ligand binds to the complex, it induces a conformational change allowing the recruitment of coactivators, histone acetyltransferases, and the basic transcription machinery.[3]

Clinical significance

Translocations that always involve rearrangement of the RARA gene are a cardinal feature of acute promyelocytic leukemia (APL; MIM 612376). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene.[4]


Retinoic acid receptor alpha has been shown to interact with:

See also


  1. ^ Giguere V, Ong ES, Segui P, Evans RM (1987). "Identification of a receptor for the morphogen retinoic acid". Nature 330 (6149): 624–9.  
  2. ^ Anderson LA, Friedman L, Osborne-Lawrence S, Lynch E, Weissenbach J, Bowcock A, King MC (September 1993). "High-density genetic map of the BRCA1 region of chromosome 17q12-q21". Genomics 17 (3): 618–23.  
  3. ^ "Entrez Gene: retinoic acid receptor". 
  4. ^ Vitoux D, Nasr R, de The H (2007). "Acute promyelocytic leukemia: new issues on pathogenesis and treatment response". Int. J. Biochem. Cell Biol. 39 (6): 1063–70.  
  5. ^ Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X, Reed JC, Zhang XK (July 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". J. Biol. Chem. 273 (27): 16985–92.  
  6. ^ a b McNamara P, Seo SB, Rudic RD, Sehgal A, Chakravarti D, FitzGerald GA (June 2001). "Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock". Cell 105 (7): 877–89.  
  7. ^ Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (February 2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". J. Biol. Chem. 278 (8): 6355–62.  
  8. ^ Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (February 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54.  
  9. ^ Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW (November 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". J. Biol. Chem. 274 (48): 34283–93.  
  10. ^ Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7.  
  11. ^ Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. 274 (22): 15901–7.  
  12. ^ Guidez F, Ivins S, Zhu J, Söderström M, Waxman S, Zelent A (April 1998). "Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia". Blood 91 (8): 2634–42.  
  13. ^ Dong S, Tweardy DJ (April 2002). "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood 99 (8): 2637–46.  
  14. ^ Hong SH, David G, Wong CW, Dejean A, Privalsky ML (August 1997). "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9028–33.  
  15. ^ Hu X, Chen Y, Farooqui M, Thomas MC, Chiang CM, Wei LN (January 2004). "Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation". J. Biol. Chem. 279 (1): 319–25.  
  16. ^ Farooqui M, Franco PJ, Thompson J, Kagechika H, Chandraratna RA, Banaszak L, Wei LN (February 2003). "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity". Biochemistry 42 (4): 971–9.  
  17. ^ L'Horset F, Dauvois S, Heery DM, Cavaillès V, Parker MG (November 1996). "RIP-140 interacts with multiple nuclear receptors by means of two distinct sites". Mol. Cell. Biol. 16 (11): 6029–36.  
  18. ^ Seol W, Choi HS, Moore DD (May 1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science 272 (5266): 1336–9.  
  19. ^ Seol W, Hanstein B, Brown M, Moore DD (October 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. 12 (10): 1551–7.  
  20. ^ Perlmann T, Jansson L (April 1995). "A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1". Genes Dev. 9 (7): 769–82.  
  21. ^ Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, Kalantry S, Freedman LP, Pandolfi PP (November 1999). "A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins". Nat. Genet. 23 (3): 287–95.  
  22. ^ Benkoussa M, Brand C, Delmotte MH, Formstecher P, Lefebvre P (July 2002). "Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter". Mol. Cell. Biol. 22 (13): 4522–34.  
  23. ^ Bugge TH, Pohl J, Lonnoy O, Stunnenberg HG (April 1992). "RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors". EMBO J. 11 (4): 1409–18.  
  24. ^ Kim HJ, Yi JY, Sung HS, Moore DD, Jhun BH, Lee YC, Lee JW (September 1999). "Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation". Mol. Cell. Biol. 19 (9): 6323–32.  
  25. ^ He B, Wilson EM (March 2003). "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs". Mol. Cell. Biol. 23 (6): 2135–50.  
  26. ^ Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D, Band H, Band V (November 2002). "Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator". J. Biol. Chem. 277 (47): 45611–8.  
  27. ^ Martin PJ, Delmotte MH, Formstecher P, Lefebvre P (September 2003). "PLZF is a negative regulator of retinoic acid receptor transcriptional activity". Nucl. Recept. 1 (1): 6.  

Further reading

  • Petkovich M, Brand NJ, Krust A, Chambon P (1988). "A human retinoic acid receptor which belongs to the family of nuclear receptors.". Nature 330 (6147): 444–50.  
  • Sirulnik A, Melnick A, Zelent A, Licht JD (2004). "Molecular pathogenesis of acute promyelocytic leukaemia and APL variants.". Best practice & research. Clinical haematology 16 (3): 387–408.  
  • Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (1992). "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling.". Nature 355 (6359): 446–9.  
  • Kastner P, Perez A, Lutz Y, et al. (1992). "Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins.". EMBO J. 11 (2): 629–42.  
  • Baniahmad A, Köhne AC, Renkawitz R (1992). "A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor.". EMBO J. 11 (3): 1015–23.  
  • de Thé H, Lavau C, Marchio A, et al. (1991). "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR.". Cell 66 (4): 675–84.  
  • de Thé H, Chomienne C, Lanotte M, et al. (1990). "The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus.". Nature 347 (6293): 558–61.  
  • Brand NJ, Petkovich M, Chambon P (1991). "Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha).". Nucleic Acids Res. 18 (23): 6799–806.  
  • Borrow J, Goddard AD, Sheer D, Solomon E (1990). "Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17.". Science 249 (4976): 1577–80.  
  • Arveiler B, Petkovich M, Mandel JL, Chambon P (1988). "A PstI RFLP for the human retinoic acid receptor in 17q21.". Nucleic Acids Res. 16 (13): 6252.  
  • Chen JD, Evans RM (1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors.". Nature 377 (6548): 454–7.  
  • Fisher GJ, Talwar HS, Xiao JH, et al. (1994). "Immunological identification and functional quantitation of retinoic acid and retinoid X receptor proteins in human skin.". J. Biol. Chem. 269 (32): 20629–35.  
  • Chen Z, Guidez F, Rousselot P, et al. (1994). "PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors.". Proc. Natl. Acad. Sci. U.S.A. 91 (3): 1178–82.  
  • Redner RL, Rush EA, Faas S, et al. (1996). "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.". Blood 87 (3): 882–6.  
  • Kamei Y, Xu L, Heinzel T, et al. (1996). "A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.". Cell 85 (3): 403–14.  
  • Liu W, Hellman P, Li Q, et al. (1997). "Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid cells.". Biochem. Biophys. Res. Commun. 229 (3): 922–9.  
  • Thénot S, Henriquet C, Rochefort H, Cavaillès V (1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1.". J. Biol. Chem. 272 (18): 12062–8.  

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